FOCMA is a transformation or tumor-specific antigen induced by the RNA containing leukemia and sarcoma viruses of cats. In experimental and field conditions FOCMA is the target for an efficient anti-tumor immune surveillance mechanism which prevents the appearance of spontaneous lymphoid malignancies. Immune surveillance operates to prevent appearance of tumors which support virus replication, and also tumors of similar histologic type which lack any evidence of virus infection per se but which nevertheless express FOCMA i.e. virus positive and virus negative leukemias. We plan to characterize the immune mechanism which prevent appearance of cat leukemias. The major assay system used will be the 51Cr release cytotoxicity assay and emphasis will be placed on using assay mixtures which contain only cat components. We will study the activity of all known immunological effector mechanisms and attempt to piece together the interaction between them. As such we will assay for naturally occurring mechanisms i.e. N.K. cells and the virolytic effect of complement, as well as immune mechanisms i.e. cellular cytotoxicity mediated by T cells and/or macrophages, antibody dependent cellular cytotoxicity and ADCC effector cell levels, virus neutralizing antibody, complement dependent antibody and complement levels. The nature and magnitude of these responses in cats will be defined before and after natural exposure (or inoculation) with leukemia or sarcoma virus, and changes following the onset of persistent viremia or appearance of tumors will be investigated. In parallel studies we will investigate the quantitative expression and crossreactivity of FOCMA on individual tumor isolates; associations between FOCMA expression and cell cycle; and aspects of the preservation of antigen expression on tumor cells rendered non-viable by various methods. These studies will provide some data necessary for development of an effective FOCMA vaccine against progressive tumor growth in cats.